Romano competed in the middleweight weightlifting division in the 1972 Olympics, but was unable to complete one of his lifts due to a ruptured knee tendon. He was due to fly home to Israel on September 6, 1972 to have an operation on the injured knee.

In the early morning hours of September 5, 1972, members of Black September broke into the Israeli quarters of the Olympic Village. After seizing the coaches in the first apartment and wounding wrestling coach Moshe Weinberg in the face, the hostage takers forced Weinberg to lead them to other potential hostages in another apartment. There, they seized six wrestlers and weightlifters, including Romano. As the athletes were being led back to the coaches' apartment, Weinberg attacked the hostage takers, which allowed wrestler Gad Tsobari to escape but resulted in Weinberg's death by gunfire. Once inside the apartment, Romano attacked the intruders, slashing Afif Ahmed Hamid in the face with a paring knife and grabbing his AK-47 away from him before being shot to death. Romano's bloodied corpse was left at the feet of his teammates all day as a warning.[1] The other nine Israeli athletes were killed during a bungled German rescue attempt later that night.[2][3]

After the death of her son, Romano's mother committed suicide. Several years later his brother did as well.[4]

Romano was portrayed by actor Sam Feuer in the 2005 film, Munich, which was directed by Steven Spielberg. After viewing the movie, Ilana Romano, Yossef's widow, said "We don't have a problem with it; the opposite, we are glad that people are being reminded of what happened in Munich so it will never happen again".

Ilana Romano fought unsuccessfully for a moment of silence to be held at the 2012 Summer Olympics in memory of the Israeli athletes murdered forty years prior.[5] In 2014, however, the International Olympic Committee agreed to contribute $250,000 towards a memorial to the dead Israeli athletes. [6]